The 10-mile section between the A5121 for Burton Upon Trent and the B5016 for Walton On Trent was blocked on the A38 southbound and closed off for several hours after the collision, which happened around 8am on Wednesday.
Officers from Staffordshire Police were called in to arrange recovery of the vehicles, while there was around 5.5 miles of congestion on the approach to the A5121 exit.
A spokesman for National Highways West Midlands said: ""The A38 in Staffordshire is now blocked southbound between the A5121 for Burton Upon Trent and the B5016 for Walton On Trent due to a multi-vehicle collision.
"Staffordshire Police are arranging recovery.
"There's now 5.5 miles of congestion on approach."
Staffordshire Police have been approached for a comment.